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In several primates and carnivores, pronation/supination angles of the forearm skeleton were examined, and it is thought that a larger angle is useful to acquire dexterous behaviors in feeding and/or life style, including climbing. In this study, the pronation/supination angles in Asiatic black, brown and polar bears were nondestructively examined. These specimens were classified as adult or non-adult. Three or four carcasses of each group of Asiatic black and brown bears were used for CT analysis, whereas only one adult polar bear was used. The forearms were positioned within the gantry of a CT scanner in both maximally supinated and pronated states. Extracted cross-sectional CT images of two positions were superimposed by overlapping the outlines of each ulna. The centroids of the radii were detected, and then the centroid of each radius and the midpoint of a line which connects between both ends of the surface of each radius facing the ulna, were connected by lines to measure the angle of rotation as an index of pronation/supination. In adult brown and polar bears, the angles were smaller as compared with the other groups (Asiatic black and non-adult brown bears). Asiatic black and non-adult brown bears can climb trees, whereas adult brown bears and polar bears cannot. This suggests that the pronation/supination angle is related to arboreal activity in Ursidae.

Background/aim The prognosis of cholangiolocarcinoma, a rare malignant liver tumor derived from hepatic progenitor or stem cells, is considered relatively good; however, it frequently recurs. We herein present the diagnosis, histological findings, and treatment of cholangiolocarcinoma. Case report A 65-year-old woman with a large liver tumor (70 mm in diameter) was referred. Hepatocellular carcinoma was suspected based on strong early enhancement and delayed washout by enhanced computed tomography. The patient underwent curative left tri-sectionectomy. Histologically, she was diagnosed with pure cholangiolocarcinoma in a slightly fibrous liver. Three metachronous recurrent lesions (all ≤10 mm in diameter) were found between fifteen and twenty months after the initial hepatectomy. One lesion and the remaining two lesions were treated with hepatectomy and radiofrequency ablation, respectively. Two years after the initial diagnosis, she was doing well without recurrence. Conclusion Repeated hepatectomy and radiofrequency ablation might be useful for small intrahepatic recurrences of cholangiolocarcinoma.

Aim To assess the utility of the perioperative use of direct oral anticoagulants for patients with hepatocellular carcinoma (HCC) with cancer-associated thrombosis. Case report An 83-year-old woman was admitted with a solitary HCC (10-cm diameter), as well as with multiple sites of venous thromboembolism and macroscopic portal vein tumor thrombosis. She had appropriate liver function without viral hepatitis, triple-positive tumor markers, and secondary polycythemia. Edoxaban at 30 mg was initiated 10 days before surgery to remove HCC. Complete remission of the pulmonary embolism and stability of the deep vein thrombosis and massive superior mesenteric vein thrombosis were recognized preoperatively. An extended left hepatectomy was successfully performed. To avoid hemorrhage complications, we used intravenous administration of nafamostat mesylate for 2 days, thereafter we restarted edoxaban. Superior mesenteric vein thrombosis resolved 5 months after surgery. Conclusion Perioperative oral administration of edoxaban was useful in multidisciplinary treatment for a patient with advanced HCC with cancer-associated thrombosis.

Background Lenvatinib, a newly developed oral multi-tyrosine kinase inhibitor, has amazing potential in the multidisciplinary treatment of advanced or metastatic hepatocellular carcinoma. Thrombocytopenia is a serious adverse event that causes drug dose reduction or withdrawal. Partial splenic embolization is currently being used as a non-surgical treatment for thrombocytopenia caused by various pharmacotherapies. Case report Partial splenic embolization was performed for three patients with hepatocellular carcinoma receiving lenvatinib therapy with/without transarterial chemoembolization. Partial splenic embolization was advantageous for various situations, including the induction of lenvatinib for patients with thrombocytopenia, application of lenvatinib after multiple transarterial chemoembolization using cisplatin and radiotherapy, and re-administration of lenvatinib after lenvatinib therapy-induced thrombocytopenia. In all cases, lenvatinib therapy was completed without need for cessation due to thrombocytopenia. Conclusion We strongly recommend the new concept of combining partial splenic embolization and lenvatinib therapy for hepatocellular carcinoma.

Background Colorectal cancer is the third most commonly diagnosed cancer in both men and women, and one of the more widely recognized preventable cancers. Adenosquamous carcinoma (ASC) of the colon/rectum is an uncommon disease that consists of both glandular and squamous components, and the most common site of ACS is the right and transverse colon. Case report Here, we present the case of a 78-year-old woman, who complained of abdominal pain. Colonoscopy revealed a circumscribed tumor in the ascending colon, and no specific lesion was detected in the other areas of the colon or rectum. ASC (pT3N0M0) was diagnosed from right hemicolectomy specimens. Three months after the first surgery, the serum levels of tumor markers had gradually increased, and a new tumor was subsequently detected in the sigmoid colon 2 months later. The sigmoid lesion was surgically resected and diagnosed as ASC (pT3N3M0). Strong PD-L1 expression was also found in the squamous component. Conclusion To our knowledge, this is the first report of a recurrent sigmoid colon ASC that likely originated from the ascending colon, and PD-L1/PD-1 signaling was likely involved in the immune escape mechanism.

In several primates and carnivores, pronation/supination angles of the forearm skeleton were examined, and it is thought that a larger angle is useful to acquire dexterous behaviors in feeding and/or life style, including climbing. In this study, the pronation/supination angles in Asiatic black, brown and polar bears were nondestructively examined. These specimens were classified as adult or non-adult. Three or four carcasses of each group of Asiatic black and brown bears were used for CT analysis, whereas only one adult polar bear was used. The forearms were positioned within the gantry of a CT scanner in both maximally supinated and pronated states. Extracted cross-sectional CT images of two positions were superimposed by overlapping the outlines of each ulna. The centroids of the radii were detected, and then the centroid of each radius and the midpoint of a line which connects between both ends of the surface of each radius facing the ulna, were connected by lines to measure the angle of rotation as an index of pronation/supination. In adult brown and polar bears, the angles were smaller as compared with the other groups (Asiatic black and non-adult brown bears). Asiatic black and non-adult brown bears can climb trees, whereas adult brown bears and polar bears cannot. This suggests that the pronation/supination angle is related to arboreal activity in Ursidae.

Background Hepatic inflammatory pseudotumor (HIPT) is an uncommon benign tumor-like mass that mimics malignant tumors. Case report A 73-year-old man was admitted with severe epigastric pain and high fever. He had received choledocojejunostomy. Enhanced computed tomography showed a 76 mm, heterogeneous, gradual enhanced low-density mass in the caudate lobe and hyperdense fluid was detected around the mass. Based on the diagnosis of hemorrhage from a hypervascular malignant liver tumor, chemoembolization was conducted. Antibiotics (Meropenem) were administered for 2 weeks, and methylprednisolone (125 mg) was administered twice as a premedication for chemoembolization. After the 2nd chemoembolization, rapid tumor shrinkage was observed and the inflammatory changes gradually disappeared. The tumor was finally diagnosed as fibrohistiocytic type HIPT with an ultrasound-guided percutaneous tumor biopsy. The diameter of the liver tumor decreased to 15 mm and intra-abdominal hemorrhage disappeared in 3 months. Conclusion Development of HIPT can be associated with intra-abdominal hemorrhage.

Aim Our aim was to confirm the utility of Indocyanine green (ICG) fluorescence imaging for intraoperative detection of adrenal hepatocellular carcinoma (HCC) metastasis. Case report An 83-year-old man with a right adrenal HCC metastasis was admitted after complete remission of primary HCC and a metachronous left adrenal metastasis. He was treated with ICG fluorescence-guided limited resection to preserve adrenal function. ICG was administered intravenously at a dose of 0.5 mg/kg, 6 days before the operation. After removal of the entire suspicious metastatic HCC, ICG fluorescence imaging clearly demonstrated two illuminated lesions. The lesions were separately resected using an energy device. Finally, there were no ICG fluorescent lesions which meant residual tumor. Histopathological examination confirmed adrenal metastasis of moderately differentiated HCC in the initial specimen and the additional resected specimens. Three months after the operation, adrenal function was well preserved without recurrence of HCC. Conclusion ICG fluorescence imaging is essential for complete resection of adrenal HCC metastasis.

Large tumor size and arterioportal shunt are poor prognostic factors for hepatocellular carcinoma. Lenvatinib is a novel and potent multi-tyrosine kinase inhibitor developed in Japan. A 66-year-old woman with hepatocellular carcinoma and untreated hepatitis C was referred to our hospital. She was judged as unresectable and was treated with four sessions of transarterial chemoembolization; however, the therapeutic effect was unsatisfactory because of major arterioportal shunt. Lenvatinib was sequentially administered for 4 months. Thereafter, we observed tumor shrinkage, complete disappearance of arterioportal shunt, and obvious improvement in liver function. A curative conversion hepatectomy was successfully accomplished. The extremely high levels of tumor markers almost normalized; the pretreatment levels were 1,008,021 ng/ml for alpha-fetoprotein. At 1 year after the primary treatment, the patient has not experienced recurrence. To our knowledge, this is the first case of a patient with initially unresectable hepatocellular carcinoma with arterioportal shunt who underwent conversion hepatectomy after multidisciplinary treatment, including lenvatinib.

Great effort has been paid to decrease blood loss during hepatectomy. Excessive blood loss and/or allogeneic blood transfusion can cause an increased risk of perioperative morbidity and mortality and may lead to a greater risk of early tumor recurrence (1-4). Hepatic steatosis or steatohepatitis is present in 30–50% of patients in the Western countries and can increase blood loss and morbidity in patients undergoing hepatectomy for colorectal liver metastases (5-7). Steatotic livers are hypertrophic and delicate and are therefore more difficult to mobilize or transect compared to nonsteatotic livers.

Gastric cancer with portal vein tumor thrombosis (GC-PVTT) is a rare condition with a very poor prognosis. A 64-year-old man with GC-PVTT was admitted to our hospital. His carcinoembryonic antigen level was slightly elevated (17.4 ng/ml). Upper gastrointestinal endoscopy showed a type-2 gastric lesion (45 mm × 40 mm) in the gastric antrum. The PVTT originated from the main gastric tumor and continued to the superior mesenteric vein. Fluorodeoxyglucose-positron emission tomography showed high uptake both by the main tumor and PVTT. A distal gastrectomy with D2 lymphadenectomy was performed with simultaneous removal of the PVTT. Pathological examination showed a poorly differentiated adenocarcinoma with neuroendocrine differentiation. Adjuvant chemotherapy with S-1 was administered for 1 year. The patient survived for >5 years with no recurrence. Surgical gastrectomy and complete removal of the PVTT followed by S-1 chemotherapy could be a treatment option that offers improved long-term survival for patients with GC-PVTT.

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Background Various pathological elbow lesions are often complicated with ulnar neuropathy at the elbow (UNE), although the precise pathology, incidence, and clinical and neurological features of these lesions have not been identified. We therefore investigated elbow pathology and neurological severity in Japanese patients with UNE. Methods The medical records of 457 Japanese UNE patients who were surgically treated among 6 hospitals were retrospectively examined. Eligible patients had UNE diagnosed by physical findings and nerve conduction studies according to the criteria of the American Association of Electrodiagnostic Medicine. The elbows were analyzed with regard to age, gender, occupation, pathology at the elbow, and severity of nerve palsy. Results A total of 398 patients with 413 UNE elbows of a mean age of 63 years (range: 15–87) met the inclusion criteria. UNE elbows were predominantly in male patients (69.0%). Overall, 310 elbows (75.1%) had 1 or more elbow lesions: 238 elbows (76.8%) had a single lesion and 72 elbows (23.3%) had 2 or more lesions. The most common lesion was primary elbow osteoarthritis (EOA) occurring in 54.5% of elbows, followed next by medial elbow ganglion in 8.5% and cubitus valgus in 6.5%. Most elbows with medial elbow ganglion or cubitus valgus were associated with EOA. Entrapment sites were at the cubital tunnel in 84.5%–91.3% of UNE elbows, regardless of an association with elbow lesion. The incidence of McGowan grade III lesion was 50.8% in elbows with primary EOA, which was higher than the 35.0% in elbows with no lesion. Conclusions This study revealed that UNE had various isolated or combined elbow lesions. In Japanese UNE, primary or secondary EOA was found in 62.2% of cases and severe motor weakness was noted in 47.2%. The incidences of EOA and severe ulnar nerve palsy in the Japanese UNE are higher than those in Caucasians. Level of evidence Level IV; Prognostic—Investigating the effect of a patient characteristic on the outcome of a disease; Case series.

Thermoplastic elastomers are attractive materials because of the drastic changes in their physical properties above and below the glass transition temperature (Tg). In this paper, we report that free-standing polystyrene (PS, Tg: 100 °C) and polystyrene–polybutadiene–polystyrene triblock copolymer (SBS, Tg: −70 °C) thin films with a thickness of hundreds of nanometers were prepared by a gravure coating method. Among the mechanical properties of these thin films determined by bulge testing and tensile testing, the SBS thin films exhibited a much lower elastic modulus (ca. 0.045 GPa, 212 nm thickness) in comparison with the PS thin films (ca. 1.19 GPa, 217 nm thickness). The lower elastic modulus and lower thickness of the SBS thin films resulted in higher conformability and thus higher strength of adhesion to an uneven surface such as an artificial skin model with roughness (Ra = 10.6 μm), even though they both have similar surface energies. By analyzing the mechanical properties of the SBS thin films, the elastic modulus and thickness of the thin films were strongly correlated with their conformability to a rough surface, which thus led to a high adhesive strength. Therefore, the SBS thin films will be useful as coating layers for a variety of materials.

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Osteoarthritis (OA) is a group of common, chronic, and painful inflammatory joint diseases. One important finding in OA patients is a remarkable decrease in the molecular weight of hyaluronic acid (HA) in the synovial fluid of affected joints. Therapeutic HA is available to patients in most parts of the world as a viscosupplementation product for the treatment of OA. Previous clinical reports show that high molecular weight HA (HMWHA) more effectively relieves pain than low molecular weight HA (LMWHA). However, the mechanism behind this finding remains unclear. In this study, we investigated whether a LMWHA (Low-0.9 MDa) and two types of HMWHA (High-1.9 MDa and 6 MDa) differentially affected chondroregulatory action. We tested this using ATDC5 cell, a murine chondrocytic cell line widely used in culture systems to study chondrogenic differentiation. We found that HMWHA, especially hylan G-F 20 (High-6 MDa), significantly induced aggrecan and proteoglycan accumulation, nodule formation, and mRNA expression of chondrogenic differentiation markers in a time- and dose-dependent manner. In addition, we showed that HMWHA prevented TNF-α induced inhibition of chondrogenic differentiation, with no effect on cell proliferation or viability. These results reveal that HMWHA significantly promotes chondrogenic differentiation of ATDC5 cells in vitro, and suggest that HMWHA plays a significant chondroregulatory role in vivo. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:1619–1627, 2014.

Laparoscopic liver resection (LLR) has become a standard procedure for hepatocellular carcinoma (HCC) as well as liver metastases and other benign and malignant liver tumors (1-3). Numerous cohort studies and their reviews or meta-analyses comparing LLR with open liver resection (OLR) for HCC frequently have serious selection biases in terms of the differences in the size, number, tumor location, and malignancy degree (4-6).

Background: The mammalian target of rapamycin (mTOR) protein is important for cellular growth and homeostasis. The presence and prognostic significance of inappropriate mTOR activation have been reported for several cancers. Mammalian target of rapamycin inhibitors, such as everolimus (RAD001), are in development and show promise as anti-cancer drugs; however, the therapeutic effect of everolimus on oesophageal squamous cell carcinoma (OSCC) remains unknown. Methods: Phosphorylation of mTOR (p-mTOR) was evaluated in 167 resected OSCC tumours and 5 OSCC cell lines. The effects of everolimus on the OSCC cell lines TE4 and TE11 in vitro and alone or in combination with cisplatin on tumour growth in vivo were evaluated. Results: Mammalian target of rapamycin phosphorylation was detected in 116 tumours (69.5%) and all the 5 OSCC cell lines. Everolimus suppressed p-mTOR downstream pathways, inhibited proliferation and invasion, and induced apoptosis in both TE4 and TE11 cells. In a mouse xenograft model established with TE4 and TE11 cells, everolimus alone or in combination with cisplatin inhibited tumour growth. Conclusion: The mTOR pathway was aberrantly activated in most OSCC tumours. Everolimus had a therapeutic effect both as a single agent and in combination with cisplatin. Everolimus could be a useful anti-cancer drug for patients with OSCC.

Laparoscopic liver resection (LLR) has become the standard treatment for various tumors of the liver including hepatocellular carcinoma (HCC) (1-3). LLR for liver tumors are considered to possess several perioperative advantages compared with conventional open liver resection (OLR). The Oslo-CoMet is the only randomized-controlled trial (RCT) to provide solid evidence that LLR is safer, less invasive, and cost-effective compared with OLR in patients with colorectal liver metastases (4).

Helium depth profiling in silicon was investigated by high-resolution elastic recoil detection analysis (HERDA) using a high-resolution Rutherford backscattering spectrometry system. A 0.7 μm Mylar film was installed in front of the detector of this system to eliminate the background signals originating from incident nitrogen ions scattered at the sample surface. This film successfully eliminated the background signals without the loss of helium signals or serious degradation of the depth resolution. The HERDA has several attractive features for helium depth profiling in silicon, including high sensitivity (detection limit of 1 at. % or less), excellent depth resolution (less than 1 nm), and good quantitative accuracy, giving it significant advantages over other surface analysis methods such as secondary ion mass spectrometry.

症例は86歳の男性で, 下血を主訴に精査を行い, 直腸内腔全体を占める全周性のRb直腸癌と診断された. 手術前の検討では肛門機能温存が不可能な低位直腸癌と診断され, 腹会陰式直腸切断術が予定されたが, 手術中に直腸癌による腸重積が判明し, これを解除することにより超低位前方切除術を行うことができた. 下部直腸癌で内腔全体を占める腫瘍の場合, 直腸癌による腸重積を考慮に入れ, 慎重な術式の選択をする必要があることが示唆された. 直腸癌による腸重積は極めてまれであり, 若干の文献的考察を加え報告する.

Surgical resection is the most effective therapy for colorectal liver metastases, subsequently there are chemotherapy and thermal destruction technique using microwave coagulation therapy (MCT) and radiofrequency ablation therapy (RFA). As the surgical approach is generally guided by these criteria (cancer factors : Tumor staging, differentiation of tumor, recurrence free interval, node status and transition of CEA. patient factors : age, liver function and performance status) and these criteria are intricated, the majority of patients present practically with unresectable. The thermal destructive therapy is well acceptable for hepatocellular cancer but not for colorectal liver metastases. We review the patients of colorectal liver metastases that we performed the thermal destructive therapy.

Objective Aldosterone plays an important role in the pathogenesis of atherosclerosis; however, the significance of mineralocorticoid receptor blockade for atherosclerosis has not been fully elucidated. In this study, the effect of add-on eplerenone on the degree of arterial stiffness was examined in patients with uncontrolled hypertension. Methods Forty-seven uncontrolled hypertensive patients who had previously been treated with anti-hypertensive drugs were examined retrospectively. Thirty-two patients received add-on therapy consisting of eplerenone (Group E) and 15 patients received add-on therapy with a Calcium channel blocker (CCB) or an increased dose of CCB (Group C) in addition to their baseline medications. Both the systolic blood pressure (SBP) and diastolic blood pressure (DBP) values were significantly decreased at two and 12 months in Group C. In contrast, neither the SBP nor DBP values were significantly changed at two months and eventually decreased at 12 months in Group E. The degree of arterial stiffness, as evaluated according to the cardio-ankle vascular index (CAVI), did not improve at either two or 12 months in Group C, whereas the CAVI values improved as early as at two months and the improvement was sustained at 12 months in Group E. The extent of change in the CAVI was not associated with the level of changes in the SBP or DBP values in Group E. Conclusion Treatment with eplerenone added to the patient's baseline medications improves the degree of arterial stiffness as early as at two months after the beginning of treatment, independent of the blood pressure-lowering actions of these drugs in patients with uncontrolled hypertension.

Introduction Rapamycin is an mTOR inhibitor with anti-tumor activity in several human cancers. However, the efficacy of this compound in osteosarcoma has not been fully elucidated. It acts downstream in the PI3K pathway and impedes cell growth, cell proliferation, cell motility, cell survival, protein synthesis and transcription. Here, we assessed the anti-tumor activity of rapamycin. We had previously reported that gemcitabine reduced viability, growth and metastasis of osteosarcoma cell lines. In this study, we investigated whether gemcitabine could enhance the anti-tumor effects of rapamycin in the murine osteosarcoma cell line LM8 in vitro and in vivo. Results In the LM8 cell line, rapamycin synergized with gemcitabine to reduce cell proliferation as determined by the WST assay and to induce apoptosis as analyzed by flow cytometry using the annexin V and 7AAD staining method. Rapamycin at doses >10 μM showed significant cytotoxicity. By combining with gemcitabine, the amount of rapamycin required for apoptosis was reduced to 1 μM. Autophagy was evaluated with the Cyto-ID® Autophagy detection kit. Not only rapamycin but also gemcitabine induced autophagy in the LM8 cell line. However, no synergistic effects were observed. Cell mobility was evaluated by migration assay using a trans-well system (LM8 cells in the upper layer and conditioned medium in the lower chamber). Rapamycin synergized with gemcitabine to reduce LM8 cell mobility. In C3H mice inoculated subcutaneously with LM8, we observed frequent metastasis to the lung. Treatment of the mice with rapamycin reduced the size of the primary tumor; elevated levels of apoptosis were observed. Moreover, rapamycin in combination with gemcitabine had additive effects on the primary tumor and almost no metastatic lesions in the lung were seen. Consequently, combination therapy prolonged the overall survival of tumor-bearing mice. Conclusions Rapamycin synergized with gemcitabine to reduce cell proliferation, and to induce apoptosis, autophagy and cell mobility of the LM8 murine osteosarcoma cell line in vitro. Rapamycin in combination with gemcitabine exhibited synergistic antitumor effects. The combination prolonged overall survival and reduced the number of lung metastases in osteosarcoma-bearing mice. Rapamycin has been used to treat osteosarcoma in clinical trials and gemcitabine combined with docetaxel chemotherapy has shown good clinical results. Rapamycin combined with gemcitabine chemotherapy might be a novel and promising therapeutic approach to the treatment of osteosarcoma. Citation Format: Takashi Ando, Jiro Ichikawa, Nobutaka Sato, Tetsuro Ohba, Kensuke Koyama, Tetsuo Hagino, Hirotaka Haro. Rapamycin in combination with gemcitabine reduced viability, growth and metastasis of the murine osteosarcoma cell line LM8 in vitro and in vivo. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3536.

p12 CDK2-associating protein 1 (p12CDK2-AP1) is a growth suppressor that negatively regulates cyclin-dependent kinase 2 (CDK2) activities. In addition, p12CDK2-AP1 has also been shown to interfere in DNA replication. A reduction of p12CDK2-AP1 expression is known to be a negative prognostic indicator in patients with oral squamous cell carcinoma. To elucidate the role of p12CDK2-AP1 expression in esophageal squamous cell carcinoma (ESCC), we immunohistochemically examined the expression of p12CDK2-AP1 protein in 120 resected ESCC specimens and determined its association with the clinicopathological characteristics and prognosis. Of the 120 ESCCs, 79 (65.8%) showed positive staining (>or=25% of cancer cells showing p12CDK2-AP1 expression), while 41 (34.2%) lacked the staining (

Purpose: MicroRNAs are ∼22 nucleotide noncoding RNA molecules that posttranscriptionally regulate gene expression. The aim of this study was (a) to determine a role of microRNA-21 in esophageal squamous cell carcinoma and (b) to elucidate the regulation of the programmed cell death 4 (PDCD4) gene by microRNA-21. Experimental Design: MicroRNA-21 expression was investigated in 20 matched normal esophageal epitheliums and esophageal squamous cell carcinomas and seven esophageal squamous cell carcinoma cell lines (TE6, TE8, TE10, TE11, TE12, TE14, KYSE30) by TaqMan quantitative real-time PCR and in situ hybridization. To evaluate the role of microRNA-21, cell proliferation and invasion were analyzed with anti–microRNA-21–transfected cells. In addition, the regulation of PDCD4 by microRNA-21 was elucidated to identify the mechanisms of this regulation. Results: Of 20 paired samples, 18 cancer tissues overexpressed microRNA-21 in comparison with matched normal epitheliums. Specifically, patients with lymph node metastasis or venous invasion showed significantly high expression of microRNA-21. In situ hybridization for microRNA-21 showed strong positive staining in paraffin-embedded esophageal squamous cell carcinoma tissues. All seven esophageal squamous cell carcinoma cell lines also overexpressed microRNA-21, and anti–microRNA-21–transfected cells showed significant reduction in cellular proliferation and invasion. The PDCD4 protein levels in esophageal squamous cell carcinoma cells have an inverse correlation with microRNA-21 expression. Anti–microRNA-21–transfected cells increased PDCD4 protein expression without changing the PDCD4 mRNA level and increased a luciferase-reporter activity containing the PDCD4-3′ untranslated region construct. Conclusions: MicroRNA-21 targets PDCD4 at the posttranscriptional level and regulates cell proliferation and invasion in esophageal squamous cell carcinoma. It may serve as a novel therapeutic target in esophageal squamous cell carcinoma.

We experienced a case of diaphragmatic hernia which occurred six years after a trauma. A 21-year-old woman underwent appendectomy under a diagnosis of acute appendicitis at a nearby hospital 3 days before. However, the patient complained of lasting abdominal pain and vomiting, was found to have a stricture of the large intestine, and was referred to our hospital. On admission tenderness of the epigastric region and weakness in breathing at lower segment of the left lung were recognized. Chest X-ray showed intestinal gas shadow in the left pleural cavity and lifting of left diaphragm.Under a diagnosis of incarceration of diaphragmatic hernia, an emergency operation was performed. Some part of the transverse colon was protruding into the left pleural cavity via the central part of the diaphragmatic tendon and was necrotic. The necrotic part of the colon was resected, and the defect of the diaphragm was sutured directly.As the patient had a history of chest and abdominal contusion by a traffic accident six years ago, she was diagnosed as traumatic diaphragmatic hernia.This case shows us a possibility that a delayed diaphragmatic hernia can occur in a certain period after chest and abdominal trauma.

Backgrounds : Esophageal squamous cell carcinoma (ESCC) is one of the most difficult malignancies to be cured among gastrointestinal tract cancers. Recently, the effect of neoadjuvant or induction chemotherapy followed by definitive local treatment for advanced ESCC has received much attention through some clinical trials. However, biomarkers which can predict the effect of chemotherapy have not yet been identified. MicroRNA (mir) is a recently discovered class of small non-coding RNAs that can regulate gene expression, and recent researches have demonstrated that changes in expression of some mirs might affect drug resistance. However, there are few reports which identified mirs related to drug resistance to ESCC, using pretreatment biopsy samples. Objective: In order to identify the mirs which can be biomarkers to predict chemosensitivity inESCC, correlation between the expression status of mirs in biopsy samples and the treatment effects has been investigated. Patients and methods: Forty patients with node-positive ESCC were eligible for this study from June 2008 to October 2009. Induction chemotherapy using Docetaxel/CDDP/5-FU (DCF) regimen (Docetaxel 60 mg/m2 on day1, 5-FU 350 mg/m2 and cisplatin 6 mg/m2 on day1-5) were given every 3 weeks for 2 courses. Tumor response to chemotherapy was evaluated by 18-F-fluorodeoxyglucose positron emission tomography(FDG-PET) before and after the chemotherapy, and decrease rate of standardized uptake value (SUV) of primary tumors during the chemotherapy has been calculated ((SUVpre - SUV post)/SUVpre X 100 (%)). When the decrease rate was more than%, the treatment was considered to be effective. Total RNA was isolated from formalin-fixed paraffin-embedded (FFPE) biopsy samples which were collected by upper gastrointestinal endoscopy. We analyzed the expression status of 28 mature mirs, which have been reported to be increased or decreased in ESCC samples or cell lines compared to normal epithelium, by Real-time quantitative RT-PCR. Results: At first, we have confirmed that expression status of mirs was preserved between FFPE biopsy samples and fresh snap tissues from patients who underwent surgery without any treatments. Among 40 patients treated with induction chemotherapy, there were 22 responders and 18 non-responders. Although 26 out of 28 mirs demonstrated similar expression profiles between responders and non-responders, mir-21and mir-26a were significantly overexpressed in FFPE biopsy samples from non-responders in compared with those from responders (P Conclusions: Expressions of mir-21 and mir-26a in the pretreatment biopsy specimens can be biomarkers to predict response to DCF in patients with ESCC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4056.

Background: Owing to refinement of an immunomagnetic separation technology method for count and characterization of circulating tumor cells (CTCs) in patients with epithelial malignancies has been established. CellSearch System (CSS) is a device using this technology and the significance of CSS has been reported in various carcinoma. On the other hand, as a novel PCR based techniques, the amplification system with transcription-reverse transcription concerted reaction (TRC) method was introduced for detecting a few cancer cells. This method amplifies a cancer-specific messenger RNA (mRNA) directly in a single tube at a constant temperature without thermal cycling in three steps for PCR: denaturing, annealing, and extension. Accordingly, this method may produce a more stable and reliable result because of its simplified process compared to conventional PCR-based techniques. Another advantage of TRC method over CSS is the cost. It takes 30 dollars per sample in TRC method, while the cost of CSS is 800 dollars per sample. Object: In this study, we have investigated the utility of TRC method which targeted CEA-mRNA in detecting CTCs of patients with colorectal cancer. Materials and Methods: Between Nov. 2008 and May 2009, 42 samples from metastatic and/or recurrent colorectal cancer patients (mCRC) were enrolled. We compared the detection rate of CTCs between TRC method and CSS. In CSS, CTC was considered as positive when at least one cancer cell was detected. On the other hand, in TRC method, CTCs was considered as positive when the result of TRC method was positive. The statistical significance was evaluated by chi-square test. Differences were considered to be statistically significant when the p-value was less than 0.05. Results: In CSS, 27 samples (64.3%) were CTC positive, while 16 samples (38.1%) were CTC positive by TRC method. All of samples which are CTC positive by TRC method were also CTC positive by CSS. In order to compensate the lower sensitivity of TRC method, we have taken serum CEA value into account. As a result, all samples negative for TRC method but positive for CSS were from the patients whose serum CEA value was more than 20 ng/ml. In contrast, when serum CEA value of the patients was less than 20 ng/ml, all samples negative for TRC method demonstrated CTC negative for CSS. These results indicate that CSS should be done only when the sample from patients whose serum CEA value is more than 20 ng/ml is negative for TRC method. Conclusions: In conclusion, combination with TRC method and serum CEA evaluation can reduce the necessity of CSS analysis and thus reduce the cost of detecting CTCs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3749.